Water Clear Cell Parathyroid Adenoma: Case Report and Literature ReviewPatrick Tassone1*, Seth Kaplan1, Lawrence Kenyon2, David Rosen1 and Edmund Pribitkin1

1Department of Otolaryngology-Head and Neck Surgery, Jefferson Medical College and Hospital, Philadelphia, USA2Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College and Hospital, Philadelphia, USA*Corresponding author: Patrick Tassone, Department of Otolaryngology-Head and Neck Surgery, Jefferson Medical College and Hospital, Philadelphia, Pennsylvania,USA, Tel: 215-955-6784; E-mail: Patrick.Tassone@jeffersonhospital.org

Rec date: March 13, 2014; Acc date: July 31, 2014; Pub date: Aug 04, 2014

Copyright: © 2014 Tassone P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Water clear cell parathyroid adenoma is a rare cause of primary hyperparathyroidism. In this rare disease entity,normal parathyroid tissue is replaced with growth of water-clear cells, instead of the chief cell hyperplasia associatedwith the majority of parathyroid adenomas. We present the case of a water clear cell parathyroid adenoma in a 54year old woman with symptomatic hypercalcemia, as well as a review of the literature on this rare disease. Thisconstitutes the 17th reported case of water clear cell parathyroid adenoma.

Keywords: Water-clear cell; Parathyroid adenoma; Primaryhyperparathyroidism

BackgroundPrimary hyperparathyroidism is the most common cause of

hypercalcemia in the ambulatory setting [1]. In 85% of cases, primaryhyperparathyroidism is due to a solitary parathyroid adenoma [1].Other causes include diffuse parathyroid hyperplasia, multipleparathyroid adenomas and, rarely, parathyroid carcinoma.

Histologically, there are several types of parathyroid adenoma, withchief cell type being the most common. Adenomas can also becomposed of oxyphil cell types, lipoadenoma or mixed cell type [2].The rarest parathyroid adenoma is the water-clear cell type, with only16 cases reported in the literature.

We present a case of primary hyperparathyroidism due to a solitarywater-clear cell parathyroid adenoma in a 54 year old woman.

Patient FindingsA 54 year old woman presented with bone pain, fatigue, depression,

weakness, and forgetfulness. Serological tests demonstratedhypercalcemia (serum calcium of 12.4 mg/dL), and an elevated serumparathyroid hormone level (PTH) of 130 ng/L indicative ofhyperparathyroidism. She had no history of kidney stones and nofamily history of endocrine neoplasia. Her head and neck examinationwas within normal limits with no palpable neck mass detected.

Preoperative neck ultrasonography revealed a normal-appearingthyroid gland and a 2.8x1.1x1.1 cm hypoechoic mass located inferiorand posterior to the left thyroid lobe consistent with a parathyroidadenoma (Figure 1).

Figure 1: Ultrasound identifies a well-defined hypoechoic massbehind the left inferior thyroid lobe.

A sestamibi scan was also consistent with a left inferior parathyroidadenoma (Figure 2). She underwent a minimally invasive radio-guidedparathyroidectomy, during which a tan 2.8 cm mass was found infero-posterior to the left thyroid lobe. The recurrent laryngeal nerve wasidentified coursing directly over the mass, which was bluntly dissectedaway from the intact nerve and removed without difficulty.Intraoperative technetium count on the mass was 1200 against abackground of 1400, and 20 minutes after removal of the mass, serumPTH had dropped from a peroperative level of 149 ng/L to 29 ng/L.The patient had an uneventful post-operative course.

Pathologic examination of the mass demonstrated a parathyroidadenoma with diffusely clear cytoplasm consistent with a water clearparathyroid adenoma (Figure 3).

Tassone, Thyroid Disorders Ther 2014, 3:3 DOI: 10.4172/2167-7948.1000160

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Figure 2: Nuclear medicine scan shows uptake consistent with leftinferior parathyroid adenoma.

Figure 3: Water clear cell parathyroid adenoma. The cells showminimal nuclear pleomorphism and have uniformly clearcytoplasm with numerous microvacuoles. Hematoxylin and eosin,original magnification 400X.

DiscussionWater clear cell parathyroid adenoma is a rare cause of primary

hyperparathyroidism; only 16 cases have been reported in theliterature. These adenomas are characterized on histology by largeclear cells, thought to be transformed from parathyroid chief cells [3].On microscopic examination, water clear cells have foamy cytoplasmcontaining vacuoles [4]. These vacuoles are typically 0.2-2 microns indiameter, and although their origin is not entirely known, they aretheorized to originate from the Golgi apparatus, endoplasmicreticulum, or mitochondria [5,6]. The transformation from normalparathyroid chief cell to vacuolated water clear-cell is speculated tooccur more frequently with advanced patient age [7,8].

Water clear cell parathyroid adenoma must be distinguished fromwater clear cell parathyroid hyperplasia, in which all four parathyroidglands have water clear cells as their dominant histology. In caseswhen all four parathyroid glands are examined microscopically, thediagnosis of water clear cell parathyroid adenoma can be readily madeif other parathyroid glands are histologically normal. For cases inwhich only one parathyroid gland is examined, as in the casepresented, the diagnosis of adenoma is made when a cuff of normalparathyroid tissue is observed around the water clear cells. Adenoma isconfirmed in other cases by resolution of hyperparathyroidismfollowing removal [9].

Among the 17 reported patients with water clear cell parathyroidadenoma, the average age at diagnosis was 57 years (range 18-81).Seven patients were male and ten female. In the 12 patients for whichultrasound were used in the imaging workup, the water clear cellparathyroid adenoma was identified in nine (75%) cases (Table 1).

In the 12 patients for which nuclear imaging were used, theadenoma was visible in seven (58%) cases. The average maximumdiameter of the adenomas reported to date was 3.8 cm (range 0.8-6.8cm).

The location of water clear cell parathyroid adenoma has varied inprevious reports. One adenoma was intrathyroidal [10] and there hasbeen one report of dual water clear cell parathyroid adenoma [5]. Allother cases, however, have reported adenomas in expected anatomicparathyroid locations. To date, water clear well parathyroid adenomashave been reported in one patient with multiple endocrine neoplasiatype 1 (MEN-1) and one patient with neurofibromatosis type 1(NF-1), but all others were sporadic.

Of note, most reported water clear cell parathyroid adenomas arerelatively large in size. Kanda et al. [9] hypothesized that water clearcells have low endocrinologic activity, and that calcium levels do notconsiderably increase until the adenoma is large. Our case of a 2.8 cmadenoma is consistent with previous reports.

Author, Year Age/Gender Calcium PTH Symptoms Ultrasound Nuclear Med Adenoma

Roth [3] 48yo M 11.8 mg/dL 4.5 mIU/mL nephrolithiasis ND ND ND

Grenko et al.[18]

40yo M 11.3 mg/dL 945 pg/mL fatigue, leg cramps ND ND 5.0 cm R superior

Begueret et al.[19]

73yo M 13.8 mg/dL 207 pg/mL nephrolithiasis ND ND 2.8 cm L inferior

Citation: Tassone P,Kaplan S,Kenyon L, Rosen D, Pribitkin E (2014) Water Clear Cell Parathyroid Adenoma: Case Report and LiteratureReview. Thyroid Disorders Ther 3: 160. doi:10.4172/2167-7948.1000160

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Dundar et al.[10]

43yo F 13.3 mg/dL 1667 pg/mL fractures, cramps, fatigue,lethargy

6 cm Lintrathyroidal

Not seen 6 cm intrathyroidal Llobe

Kuhel et al. [5] 56yo F 3.3 mmol/L 52 ng/L asymptomatic 2.3 cm R thyroid Not seen 2.8 cm R superior,1.5 cm L superior

Kanda et al. [9] 52yo F 11.7 mg/dL 672 pg/mL nephrolithiasis 2.6 cm L inferior L inferior 6.8 cm L inferior

Prasad et al.[20]

40yo F 12.4 mg/dL 346 pg/mL fatigue, cramps, weakness ND ND 3.0 cm L superior

Kodoma et al.[16]

18yo F 11.6 mg/dL 356 pg/mL nephrolithiasis 4.5 cm R Right 5.0 cm R superior

Liang et al. [17] 59yo F 11.8 mg/dL 265 pg/mL mood changes,

lethargy

Not seen L superior, Rsuperior

4.5 cm R superior

Papanicolau-Sengos et al.[11]

64yo M normal ND asymptomatic ND ND 4.7 cm L inferior

Bai et al. [6] 81yo M ND 22.2 pmol/L ND Not seen Lower neck 4.0 cm R superior

Bai et al. [6] 55yo M ND 15.9 pmol/L ND Not seen Not seen 1.4 cm L superior

Piggott et al.[14]

74yo F 3.13 mmol/L 488.9 ng/L abd pain,

constipation, lethargy

4.8 cm L inferior L inferior 5.5 cm L inferior

Ezzat et al. [15] 73yo M 3.24 mmol/L 30.8 pmol/L ND L inferior L inferior 3.7 cm L inferior

Ezzat et al. [15] 74yo F 2.9 mmol/L 11.8 pmol/L ND 1.6 cm L inferior Not seen ND

Murakami et al.[4]

59yo F 11.9 mg/dL 72.3 pg/dL nephrolithiasis, gastric ulcer 0.8 cm L Not seen 0.8 cm L inferior

Present Case 54yo F 12.4 mg/dL 130 ng/L bone pain, fatigue,depression, weakness,forgetfulness

2.8 cm L inferior L inferior 2.8 cm L inferior

Table 1: Seventeen reported cases of water clear cell parathyroid adenoma.

The differential diagnosis for water clear cell parathyroid adenomaincludes metastatic renal cell carcinoma (RCC), clear cell type [6]. Thetwo entities appear histologically similar, and water clear cells havebeen reported to stain positively with an RCC monoclonal antibody[6,11]. Further confusing the clinical picture is the fact that RCC cansynthesize PTH-related protein and produce the hypercalcemia morecommonly seen with parathyroid adenoma [12,13]. These findingsstress the importance of a thorough history and physical examinationin the workup of any case of primary hyperparathyroidism.

The clinical presentation of patients with water clear cell adenomais indistinguishable from that of the more common parathyroidadenoma, and the diagnosis is made only on pathologic examination.To date, there have been no reports following complete excision. Withmore cases of water clear cell parathyroid adenoma identified andreported, this rare cause of hyperparathyroidism can be morecompletely characterized.

In summary, we report the case of a 54 year old female patient withprimary hyperparathyroidism caused by a water clear cell parathyroidadenoma. Water clear cell adenomas are a rare cause ofhyperparathyroidism, which can be considered cured after theircomplete surgical removal.

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Citation: Tassone P,Kaplan S,Kenyon L, Rosen D, Pribitkin E (2014) Water Clear Cell Parathyroid Adenoma: Case Report and LiteratureReview. Thyroid Disorders Ther 3: 160. doi:10.4172/2167-7948.1000160

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11. Papanicolau-Sengos A, Brumund K, Lin G, Hasteh F (2013) Cytologicfindings of a clear cell parathyroid lesion. DiagnCytopathol 41:725-728.

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Citation: Tassone P,Kaplan S,Kenyon L, Rosen D, Pribitkin E (2014) Water Clear Cell Parathyroid Adenoma: Case Report and LiteratureReview. Thyroid Disorders Ther 3: 160. doi:10.4172/2167-7948.1000160

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